Seeding Human Mesenchymal Stem Cells into Fibrin-Based Scaffolds - A Potential for a Future Angiogenic Therapy?

Abstract

Experimental studies have demonstrated that mesenchymal stem cells (MSCs) can induce neovascularization and improve heart function in ischemic myocardium. There is evidence to suggest that these cells can promote angiogenesis, presumably on account of the “paracrine effect”. A main obstacle to effective cell therapy is the lack of an optimal cell delivery technique. Furthermore, recipient ischemic tissue may be inadequate for retention of donor cells in sufficient quantity to allow for the desired effect. Cell-based angiogenesis may, therefore, benefit from tissue engineering strategies for the purpose of improving the administration of cells and optimizing their specific homing. In this study, we have generated and expanded human MSCs from bone marrow (BM), and controlled their differentiation under different conditions. Furthermore, a bioreactor system was designed and built to impart cyclic strains onto the cell-seeded fibrinbased scaffold in vitro, evaluating the possible effects on its incorporated cells. Our results showed that human MSCs can be induced to express, in vitro, markers of the endothelial lineage and function in a fibrin-based scaffold. We found that the cells, seeded in scaffolds in a bioreactor, obtained greater viability, and expressed the same level of endothelial markers compared to cells plated on conventional lab surfaces. It is therefore postulated that fibrin-based scaffold may have potential as a biomaterial scaffold and MSC-seeded fibrin scaffolds may be an alternative to cellular transplantation of BM stem cells (BMSc) as future angiogenic therapy.